SKLB023 is a potent small-molecule inhibitor of inducible nitric oxide synthase (iNOS) with IC50 of 8.66 uM, exhibits excellent anti-inflammatory activity in arthritis and antifibrotic effects in renal interstitial fibrosis.
SKLB023 inhibits iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE(2) production (IC(50) = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells.
SKLB023 inhibits the TGF-β1-induced activation of hepatic stellate cells (HSCs) LX-2 with IC50 of 36.06 and 19.48 μM after 24 and 48 h, respectively.
SKLB023 inhibits TGF-β1-induced Smad2/3 phosphorylation in vitro.
SKLB023 (50 mg/kg, oral administration) possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
SKLB023 blocks joint inflammation and cartilage destruction in arthritis models via suppression of nuclear factor-kappa B activation in macrophage.
SKLB023 hinders renal interstitial fibrosis in obstructive nephropathy by interfering TGF-beta1/Smad3 signaling.